Ecstasy is a widely used drug that reportedly has unique effects, distinct from other stimulants;most notably it is said to increase feelings of empathy and closeness to others. These so-called 'empathogenic'effects on social and emotional processing appear to contribute to the widespread recreational use of the drug, as well as its purported utility as an aid in psychotherapy. The main psychoactive constituent of ecstasy is 13,4- methylenedioxymethamphetamine (MDMA), which acts on serotonin and dopamine, two neurotransmitter systems integrally involved in modulation of affect and reward. In this project, we propose to investigate dimensions of social and emotional processing that may contribute to the putative 'empathogenic'effects of MDMA. We will study the effects of MDMA (0, 1.0 and 1.5mg/kg) on emotional recognition and emotional responsivity, both central aspects of social and emotional processing, and on sociability. On measures of emotional recognition, we hypothesize that MDMA will reduce recognition of negative or threatening emotions, such as fear, anger and sadness. Conversely, we expect MDMA to enhance emotional responsivity to positive material. On aspects of sociability, we hypothesize that the drug will enhance perception of social targets as friendly and attractive, and increase the motivation to engage in a social activity. We will also conduct exploratory investigations to identify sources of individual differences in subjective and physiological response to MDMA, including differences associated with gender and selected genotypes. In a single, double-blind, placebo controlled study, healthy volunteers (N=100) with a history of ecstasy use will be tested with MDMA and two active control drugs, methamphetamine (MA;20mg) and oxytocin (OT, 20 IU). MA shares many psychostimulant properties with MDMA but does not appear to exert 'empathogenic'effects, whereas OT appears to produce certain pro-social effects that resemble those attributed to MDMA. The proposed study is highly innovative because it applies state-of-art techniques from social neuroscience to investigating processes involved in the rewarding effects of drugs (see McGregor et al., 2008;Schnur and Shurtleff, 2008). This project will potentially broaden our perspective on how drugs interact with the social and emotional context in which they are used, and how these interactions influence vulnerability to repeated or compulsive use of these drugs. PUBLIC HEALTH RELEVANCE: Ecstasy is a widely abused drug that appears to have unique psychological effects including feelings of empathy and closeness to others. This study will assess the effects of MDMA, the active drug in ecstasy, on both behavioral and subjective measures of emotional processing and sociability in humans. The study has implications for basic science to identify the brain circuits involved in social and emotional processing. It has public health implications by helping researchers understand why people use ecstasy, and some clinicians have suggested that MDMA might facilitate emotional processing during psychotherapy.